A5103110924- Sphingolipid Metabolism and Signaling
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid Membrane Structure and Behavior
- T-cell and B-cell Immunology
- Endoplasmic Reticulum Stress and Disease
- Pain Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Genomic variations and chromosomal abnormalities
- Cancer-related gene regulation
- Protein Kinase Regulation and GTPase Signaling
- Inflammasome and immune disorders
- NF-κB Signaling Pathways
- Neuroscience and Neuropharmacology Research
- Reproductive System and Pregnancy
- TGF-β signaling in diseases
- Homelessness and Social Issues
- Gene expression and cancer classification
- Multiple Sclerosis Research Studies
- Hereditary Neurological Disorders
- Immune Response and Inflammation
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
University of South Florida
2025
University of California, Irvine
2024
Icesi University
2024
Sanford Burnham Prebys Medical Discovery Institute
2018-2023
Discovery Institute
2018-2023
Scripps Research Institute
2006-2020
Arizona State University
2014
University of California, San Diego
1993-2011
University of Puerto Rico at Río Piedras
1990
The University of Texas Southwestern Medical Center
1978
Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms sclerosis. Its mechanism action is thought be immunological active phosphorylated metabolite, FTY720-P, that resembles S1P and alters lymphocyte trafficking receptor subtype 1 . However, previously reported expression in vitro studies receptors suggested direct CNS effects might theoretically...
The signaling effects of lysophospholipids such as lysophosphatidic acid (LPA) are mediated by G protein-coupled receptors (GPCRs). There currently four LPA known LPA(1-4). Genetic deletion studies have identified essential biological functions for in mice. However, these also revealed phenotypes consistent with the existence yet unidentified receptors. Toward identifying new receptors, we screened collections GPCR cDNAs using reverse transfection and cell-based assays. Here report an...
During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified strain, designated Duane, which NK cells were reduced and spleen but increased lymph nodes (LNs) bone marrow (BM). The accumulation of LNs reflected decreased ability to exit into lymph. This strain carries point mutation within Tbx21 (T-bet), generates defective protein. Duane have 30-fold deficiency sphingosine-1-phosphate receptor 5 (S1P5) transcript levels,...
The E2A gene encodes the E47 and E12 basic helix-loop-helix (bHLH) transcription factors. T cell development in E2A-deficient mice is partially arrested before lineage commitment. Here we demonstrate that expression becomes uniformly high at point which thymocytes begin to commit towards lineage. protein levels remain until double positive developmental stage, they drop relatively moderate levels, are further downregulated upon transition single stage. However, stimuli mimic pre-T receptor...
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that signals through G protein-coupled receptors (GPCRs) to produce range of biological responses. A recently reported fourth receptor, LPA4/GPR23, was notable for its low homology the previously identified LPA1–3 and ability increase intracellular concentrations cAMP calcium. However, signaling pathways leading LPA4-mediated induction calcium levels have not been reported. Using epitope-tagged LPA4, pharmacological intervention,...
Blockade of lysophosphatidic acid signaling provides a new strategy for treating fetal hydrocephalus.
Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism unknown function. In this study, we report altered in single, sporadic Alzheimer's disease (AD) characterized by increases DNA content and amyloid precursor protein (APP) gene copy number. AD cortical nuclei displayed large variability with average ∼8% over non-diseased controls were unrelated to trisomy 21. Two independent single-cell number analyses identified amplifications at APP locus....
Hearing requires the transduction of vibrational forces by specialized epithelial cells in cochlea known as hair cells. The human ear contains a finite number terminally differentiated that, once lost noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1-phosphate (S1P) signaling, mainly via activation its cognate receptor S1P 2 , is required for maintenance vestibular and cochlear vivo . Two receptors, 3 were found to expressed reverse...
Abstract It is widely assumed that the human brain contains genetically identical cells through which postgenomic mechanisms contribute to its enormous diversity and complexity. The relatively recent identification of neural throughout neuraxis showing somatically generated mosaic aneuploidy indicates vertebrate can be genomically heterogeneous (Rehen et al. [2001] Proc. Natl. Acad. Sci. U. S. A. 98:13361–13366; Rehen [2005] J. Neurosci. 25:2176–2180; Yurov [2007] PLoS ONE:e558; Westra...
We used a DNA-protein interaction screening method to isolate cDNA, Erg-3, whose product binds site, designated pi, present in the immunoglobulin (Ig) heavy-chain gene enhancer. Erg-3 is an alternatively spliced of erg and contains Ets DNA-binding domain. Fli-1 PU.1, related proteins, also bind same site. In addition, PU.1 second microB, Ig demonstrate that pi binding site crucial for enhancer function. we show Fli.1, but not can activate reporter construct containing multimer...
Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate E2A+/− cells express an autoreactive cell receptor fail mature due in part inability activate secondary immunoglobulin (Ig) light chain rearrangement. Both RAG1/2 expression and RS deletion severely defective mice. Additionally, mice show increase proportion of marginal zone with a concomitant decrease follicular cells. In contrast, Id3-deficient splenocytes decline...
Schwann cell (SC) migration is an important step preceding myelination and remyelination in the peripheral nervous system, can be promoted by peptide factors like neuregulins. Here we present evidence that a lipid factor, lysophosphatidic acid (LPA), influences both SC through its cognate G protein-coupled receptor (GPCR) known as LPA1. Ultrastructural analyses of nerves mouse null-mutants for LPA1 showed delayed SC-to-axon segregation, polyaxonal single SCs, thinner myelin sheaths. In...
Astrocytes have prominent roles in central nervous system (CNS) function and disease, with subpopulations defined primarily by morphologies molecular markers often determined cell culture. Here, we identify an
Somatic copy number variations (CNVs) exist in the brain, but their genesis, prevalence, forms, and biological impact remain unclear, even within experimentally tractable animal models. We combined a transposase-based amplification (TbA) methodology for single-cell whole-genome sequencing with bioinformatic approach filtering unreliable CNVs (FUnC), developed from machine learning trained on lymphocyte V(D)J recombination. TbA–FUnC offered superior genomic coverage removed >90% of...